Triethylamine → N'-{(1s,2r)-1-(3,5-Difluorobenzyl)-2-Hydroxy-3-[(3-Methoxybenzyl)amino]propyl}-5-Methyl-N,N-Dipropylisophthalamide

HRID 348804

反応式

HRID 348804 の反応式
FC(F)(F)C(O)=O.[NH2:8][C@@H:9]([CH2:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=1)[C@H:10]([OH:22])[CH2:11][NH:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=1.C(N(CC)CC)C.[CH3:39][C:40]1[CH:41]=[C:42]([C:49]([N:51]([CH2:55][CH2:56][CH3:57])[CH2:52][CH2:53][CH3:54])=[O:50])[CH:43]=[C:44]([CH:48]=1)[C:45](O)=[O:46].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[F:31][C:26]1[CH:25]=[C:24]([CH:29]=[C:28]([F:30])[CH:27]=1)[CH2:23][C@H:9]([NH:8][C:45](=[O:46])[C:44]1[CH:48]=[C:40]([CH3:39])[CH:41]=[C:42]([C:49]([N:51]([CH2:52][CH2:53][CH3:54])[CH2:55][CH2:56][CH3:57])=[O:50])[CH:43]=1)[C@H:10]([OH:22])[CH2:11][NH:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=1

参加物

7

反応物 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 113913935-methyl-N,N-dipropylisophthalamic acidHCID 69869154(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol Trifluoroacetate

生成物 1

HCID 9916309N'-{(1s,2r)-1-(3,5-Difluorobenzyl)-2-Hydroxy-3-[(3-Methoxybenzyl)amino]propyl}-5-Methyl-N,N-Dipropylisophthalamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol trifluoroacetate salt (VIII, EXAMPLE 5) is dissolved in anhydrous DMF (3 mL) and cooled to 0 degrees C. Triethylamine (500 microliter, 3.6 mmol) and 5-methyl-N,N-dipropylisophthalamic acid (156 mg, 0.59 mmol) are added with stirring. The mixture is warmed to 20–25 degrees C. briefly to allow for complete dissolution of the carboxylic acid, before recooling to 0 degrees C. 1-Hydroxybenzotriazole (157 mg, 1.2 mmol) is added with stirring, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (229 mg, 1.2 mmol). The resulting mixture is stirred at 0 degrees C. for 5 minutes, then warmed to 20–25 degrees C. for 15 hours. The reaction mixture is then quenched with aqueous citric acid (10%), and the mixture extracted three times with ethyl acetate. The combined organic extracts are washed with saturated sodium bicarbonate, saline, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the the title compound in crude form. This material is purified by flash chromatography (2–10% methanol/methylene chloride gradient elution) to give purified title compound, MS (ES) MH+=582.3.

後処理

  1. temperatureThe mixture is warmed to 20–25 degrees C
  2. custombefore recooling to 0 degrees C
  3. stirringwith stirring
  4. stirringThe resulting mixture is stirred at 0 degrees C
  5. temperaturewarmed to 20–25 degrees C
  6. waitfor 15 hours
  7. customThe reaction mixture is then quenched with aqueous citric acid (10%)
  8. extractionthe mixture extracted three times with ethyl acetate
  9. washThe combined organic extracts are washed with saturated sodium bicarbonate, saline
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-59b084bab50d4b05bfbe432e04e7c6c9
出典データセット
uspto-grants-2007_02
特許番号
US07176242B2

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